Alpha-halogenosulfamylacetophenones



United States Patent r 2,126,264 ALPHA-HALOGENOSULFAMYLACETORHENONESWalter A. Gregory, Wilmington, Del., assignor to E. I. du Pont deNemours and Company, Wilmington, Del., a corporation of Delaware NoDrawing. Application May 27, 1954, Serial No. 432,889

12 Claims. (Cl. 260-556) This invention toalpha-halogenosulfamylacetophenones of the kind more particularlydescribed below and to their preparation.

The alpha-halogenosulfamylacetophenones of the invention are representedby the formula 1 R l a O R @Jl-omar where R1 and R2 are the same ordifferent and represent hydrogen, lower alkyl or hydroxyethyl radicals,R3 is hydrogen, halogen, lower alkyl or lower alkoxyl radicals, and X isa halogen of the class consisting of chlorine, bromine and iodine.

By the terms lower alkyl and lower alkoxy, I mean to include all alkyland alkoxy radicals containing up to but not exceeding 6 carbon atoms.

Illustrative of the compounds of the present invention there can benamed the following:

The'compounds of the present invention can be prepared by reacting anitrogen containing compound of the formula where R; and R have the samesignificance as in formula 1 with an ethylbenzenesulfonyl halide of theformula 7 C Ha C H2 S O z-halogen 2,726,264 Patented Dec. 6, 1955 whereR: has the same significance as in formula 1 to give asulfamylethylbenzene of the formula which in turn is oxidized to give ;asulfamylacetophenone of the formula The compound of Formula 5 is thenhalogenated, in, a solvent such as chloroform, methylene chloride,ethylene chloride or glacial acetic acid, to give a compound of Formula1.

This preparative schememay be represented diagrammatically as follows: 1

2 Alternatively, the sulfamylphenacyl halides of my invention can beprepared from a fluorosulfonylacetophenone: of the formula where X ishalogen such as chlorine or fluorine, by mixing a compound of Formula 6with a compound of Formula 2, and halogenating the resultingsulfamylacetof phenone.

Compounds represented by Formula 6 are readily available from either oftwo types of chemical structures,

namely,

Potassium permanganate and magnesium nitrate hexahydrate may be used toconvert a compound of Formula 7 to a compound of Formula 6. It ispreferred to add an acetone solution of the fluoride to an aqueoussystem containing potassium permanganate and magnesium nitrate.Compounds -of Formula -8 can be converted -to those of Formula 6 by useof potassium fluoride, or potassium bifluoride and water.

The reaction between .the nitrogen-containing compound of Formula 2 andthe fluorosulfonylacetophenone of Formula 6 is preferably carried out byadding the acetophenone to the nitrogen-containing compound of Formula2. The reactants are then thoroughly mixed for a period of, say, aboutminutes, or until solution is completed. The resulting mixture may thenbe concentrated, or diluted with water, to 'yieldafter the excess basehas been neutralized with acida compound, which 'upon halogenation,gives the desired product.

The compounds of the present invention 'are useful in the preparation ofother organic compounds, such as for instance, the substituted andunsubstituted sulfamylphenylamido-l,3-propanediols of my copendingparent application, Serial .No. 296,959, filed July 2, 1952, now PatentNo. 2,680,135.

My novel compounds are antifungal agents and find use in the control ofAlternaria solani. The meta and ortho sulfamylphenacyl halides of myinvention which are unsubstituted on the nitrogen or substituted withone alkyl group form useful polymers in basic media.

In order to more fully understand the invention, reference should be hadto the following illustrative examples:

EXAMPLE 1 Alpha-br mo-p-(dimethylsulfamyl)acetophenone To a stirredsolution of 640 g. of dimethylamine in 2 liters of water at 10 C. thereis added 990 g. of p-ethylbenzenesulfonyl chloride. The temperature ofthe reaction mixture is kept between 10-15" C. during the chlorideaddition. At the end of the addition the temperature of the mixture israised to 40 C. and maintained at 40 C. for a period of one-half hour.The resulting solution is cooled and then extracted with chloroform. Thechloroform extract is distilled. The product,p-dimethylsulfamylethylbenzene, is collected at a temperature of from178-180 C. at 10 mm. pressure. It is a white crystalline solid "melting49-51 C.

The yield of p-dimethylsulfamylethylbenzene is864 g. The formula ofp-dimethylsulfamylethylbenzene is shown Asolution of 800 ,g. ofp-dimethylsulfamylethylben-. zene in 9.5 liters of acetone is added to amixture consisting of 570 g. of potassium permanganateand 1530 ,g. ofmagnesium nitrate hexahydrate in 9.5 liters of water warmed -to atemperature of 50 C. The reaction mixture is stirred at a temperature of.50" C. for a periocl of two hours. Then an additional 220 g. ofpotassium permanganate is added. The reaction is allowed to continue forthree hours.

The excess permanganate is reduced by adding sodium sulfite until thefiltered solution is .colorless. The manganese dioxide is removed byfiltering the solution with the use of Celite Filter Aid. The filtrate,which is sepa- .ratedas a semi-crystalline mass, amounts to 794 g. Iheproduct can be purified by successive crystallizations from carbontetrachloride or benzene, or it may be distilled under reduced pressure.A substantial quantity of unoxidized starting material is recovered. Theproduct, pdimethylsulfamylacetophenone, is a white crystalline solidmelting 102-103 C., and has the following structural formula:

Ns0.@b-om Analysis.--Calcd. for CmHisNOsS: C, 52.84; H, 5.76; N, 6.16.Found: C, 52.79; H, 5.88; N, 6.07.

A solution of 261 g. of p-dimethylsulfamylacetophenone in 1.5 liters ofglacial acetic acid is stirred at a temperature of 17-20" C. as 183.8 g.of bromine is added. An initial induction period is required for thebromination to start. This varies from 15 minutes to several hours.After the solution decolorizes, the bromine is added dropwise over aperiod of two hours. The resulting mixture is then poured into 5 litersof ice and water. The product separates as an oil, which sooncrystallizes. The product amounts to 349 g. and has a melting range of7580 C. After the crude product is recrystallized twice from benzene,244 g. of white crystalline material is obtained. M. P. -92 C.Additional product is recoverable from the filtrate.

The product, alpha-bromo-p-(dimethylsulfamyl)-acetophenone, has thefollowing structural formula:

0H3 Analysis.-Calcd. for CmHmBrNOzS: Br, 26.01. Found: Br, 25.91.

EXAMPLE 2 Alpha-chl r0-m-sulfamylacet0phen0ne O iCHzC1 Oz-NH:

A 50 g. portion of m-chlorosulfonylacetophenone prepared fromacetophenone oand m-sulfonic acid sodium salts by the method which isdescribed in Example 2 ofmy copending United States application, SerialNo. 431,291, filed May 20, 1954, is added with stirring to cc. ofconcentrated aqueous ammonia. The temperature of the reaction mixture iskept below 30 C. and stirring of the mixture is continued for a periodof 24 hours. The solution is concentrated under reduced pressure, andthe residue is taken up in water and the solution adjusted to pH 4. Theproduct crystallizes from the water, and may be purified byrecrystallization from water. This product is .m-sulfamylacetophenone,and .has the formula A mixture of 40 g. of m-sulfamylacetophenone with200 cc. of glacial acetic acid is stirred at 25 C. as 14 g. of chlorine.is boiled into the mixture during a two hour period. The reaction iscontinued for one hour, and the mixture is then poured upon ice andwater. The product separates as white crystals and may be purified byrecrystallizing from nitromethane.

EXAMPLE 3 Alpha-br0m0-0-(methylsulfamyl) acetophenone SO2-NCHz A 200 cc.portion of 25% aqueous methyl amine is stirred and kept between l530 C.as 70 g. of o-fluorosulfonylacetophenone is added. Stirring is continued30 minutes at the end of the addition, and the excess methyl amine isremoved by concentrating the solution under reduced pressure. Theresidue is diluted with Water, and the solution made acid with dilutehydrochloric'acid. The product, o-(methylsulfamyl)acetophenone, may bepurified by distillation under reduced pressure. The structure of theproduct is A solution of 64 g. of o-(methylsulfamyl)acetophenone in 200cc. of methylene chloride is stirred at 20 C. as 48 g. of bromine isadded slowly thereto. After an initial induction period, he bromine isdecolorized rapidly, and the addition is then made over a two-hourperiod. Onehalf hour after the addition is complete, the product may beisolated by distilling the methylene chloride oif under reducedpressure.

EXAMPLE 4 Alpha-bromo-p-(Z-hydroxyethylsulfamyl) acetophenone A solutionof 300 g. of ethanolamine in 500 cc. of water is stirred as 200 g. ofp-chlorosulfonylacetophenone is added slowly. The temperature of thereaction mixture is kept below 25 C. After the addition is complete, themixture is stirred 30 minutes. The solution is made acid withhydrochloric acid, and the product separates as a crystalline solid. Itmay be purified by recrystallizing it from Water. The product isp-(2-hyroxyethylsulfamyl)acetophenone and has the structure A mixture of73 g. of p-(Z-hydroxyethylsulfonyl)- acetophenone and 300 cc. of glacialacetic acid is stirred at 20 C. as 48 g. of bromine is slowly added. Atfirst the bromine is not decolorized due to an induction period. Afterthe bromination is started, the addition is made over two hours. At theend of the bromination, the mixture is poured into ice and water, andthe product separates as a crystalline solid. It may be purified bycrystallization from ethanol.

I claim: 1. A compound of the formula R: Q l R1 -C--CH2X Where R1 and R2are members of the class consisting of hydrogen, lower alkyl andhydroxyethyl radicals, R3 is a member of the class consisting ofhydrogen, halogen, lower alkyl and lower alkoxy radicals, and X is ahalogen of the group consisting of chlorine, bromine and iodine.

2. Alpha-bromo-p-(dimethylsulfamyl)acetophenone.

3. Alpha-bromo-p-(methylsulfamyl)acetophenone.

4. Alpha-bromo-p-sulfamylacetophenone.

5. Alpha-chloro-p-sulfamylacetophenone.

6. Alpha-chloro-p- (methylsulfamyl) acetophenone.

7. A process which comprises the steps of mixing a compound of theformula Q-omom o halogen- S 0 where R3 is a member of the classconsisting of hydrogen,

halogen, lower alkyl and lower alkoxy radicals, with a compound of theformula where R1 and R2 are members of the class consisting of hydrogen,lower alkyl and hydroxyethyl radicals, to yield a compound of theformula oxidizing the latter compound with potassium permanganate andmagnesium nitrate to obtain a compound of the formula 1 -iJ-CHa 0 N-Shalogenating the latter compound, and recovering a compound of theformula where Rr and R2 are members of the class consisting of hydrogen,lower alkyl and hydroxyethyl radicals and R3 is a member of the classconsisting of hydrogen, halogen, lower alkyl and lower alkoxy radicalswith a halogen of the class selected from chlorine, bromine and iodineto obtain a compound of the formula where R1, R2, R3 have the samesignificance as above and X is a member. of the class consisting ofchloro, bromo and iodo radicals.

10. A process of claim 9 wherein the halogen and sulfamylacetophenoneare brought into contact with each other in the presence of an organicsolvent.

11. A process of claim 10 wherein the solvent is glacial acetic acid.

12. A process of claim 11 where the solvent is a lower alkylenechloride.

References Cited in the file of this patent UNITED STATES PATENTSGregory June 1, 1954 Gregory June 1, 1954

1. A COMPOUND OF THE FORMULA